SLC6A2 variants may predict remission from major depression after venlafaxine treatment in Han Chinese population

Venlafaxine, an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) type, is used to treat patients with major depressive disorder (MDD). Much evidence suggests that genetic polymorphisms may modulate serotonergic and noradrenergic function, thereby affecting the treatment efficacy of venlafaxine. The aim of this study was to examine whether polymorphisms in the norepinephrine transporter gene (SLC6A2) associate with remission after venlafaxine treatment for MDD.

An 8-week naturalistic treatment study with venlafaxine was carried out in 243 Han Chinese patients with MDD. The patients were screened for seven single-nucleotide polymorphisms of the SLC6A2 gene. Of the enrolled patients, 161 completed the 8-week treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was used to assess the improvement of depressive symptoms in each subject from baseline to the endpoint. For better presentation of time-course change of remission status, a Cox regression analysis for remission incidence during the 8-week treatment was conducted.

Between remitters and non-remitters, significant differences in genotype frequencies were observed in five of the investigated SLC6A2 variants (rs28386840, rs1532701, rs40434, rs13333066, rs187714). GCG haplotype (rs40434 - rs13333066 - rs187714) in the SLC6A2 gene showed a association with non-remission. A Cox regression analysis for remission incidence during the 8-week treatment course significantly depends on SLC6A2 variants (rs28386840, rs40434, and rs187714).

Our results suggest that the variation of the SLC6A2 gene is associated with treatment remission after venlafaxine in patients with MDD.